Why Clinical Laboratories Should Consider Weighing In on CMS and CDC’s New CLIA Request for Information

An opportunity for laboratories to help shape the future of CLIA regulation

On July 16, 2026, the Centers for Medicare & Medicaid Services (CMS) and the Centers for Disease Control and Prevention (CDC) issued a Request for Information (RFI) seeking stakeholder input on potential updates to the Clinical Laboratory Improvement Amendments of 1988 (CLIA) regulations. Comments are being accepted through September 14, 2026. For many laboratory leaders, an RFI can seem like just another government notice. However, this particular request represents one of the most significant opportunities in years for laboratories to influence how CLIA evolves to address modern testing technologies, new operational models, artificial intelligence, cybersecurity, molecular diagnostics, and other advances that simply did not exist when the current regulations were developed.

Why Is CMS Requesting Information?

The current CLIA regulations were implemented in 1992. Since then, laboratory medicine has undergone significant transformation. Technologies such as next-generation sequencing (NGS), molecular diagnostics, AI-assisted interpretation, cloud-based analytics, digital pathology, and advanced laboratory-developed testing have become routine components of modern laboratory practice. CMS and CDC specifically noted that laboratory testing technology has advanced significantly since CLIA regulations were first implemented and are seeking input on whether updates are warranted. CMS and CDC are gathering information to determine whether future rulemaking should occur and, if so, what areas should be prioritized. The laboratory community therefore has a unique opportunity to help regulators understand current practices, challenges, and unintended consequences before any regulatory changes are proposed.

What Topics Are Being Discussed?

The RFI focuses on several broad categories:

1. Emerging and Specialty Testing Technologies

CMS is seeking feedback on areas that are either not clearly addressed or were largely unforeseen when CLIA regulations were created, including:

• Clinical breath testing
• Next-generation sequencing
• Minimal residual disease (MRD) testing
• Methylation testing
• Pharmacogenomics
• Histocompatibility testing
• AI-assisted interpretation
• Data-only testing and interpretation facilities

For laboratories performing advanced molecular and genomic testing, this represents an important opportunity to educate regulators about contemporary workflows, validation approaches, and quality oversight mechanisms.

2. Laboratory Operations and Quality Processes

The RFI includes specific questions regarding:

• Pathology block retention periods
• Specimen preparation activities
• Personnel qualifications and training
• Handling suboptimal specimens
• Establishment of performance specifications
• Calibration verification challenges
• Competency assessment practices

These operational areas affect laboratories daily and could ultimately influence future compliance expectations.

3. Artificial Intelligence and Digital Health

One of the most forward-looking sections asks laboratories how they are currently utilizing AI and software tools in post-analytic interpretation and reporting. CMS is seeking information on:

• AI-assisted result interpretation
• Digital pathology applications
• Cloud analytics
• Software validation approaches
• Technology considerations for high-complexity testing

As AI adoption accelerates, laboratory feedback will be critical in helping CMS distinguish between innovation that improves patient care and technologies that may require additional oversight.

4. Emergency Preparedness, Biosafety, and Cybersecurity

Recent public health emergencies and increasing cyber threats have highlighted vulnerabilities across healthcare infrastructure. CMS is therefore gathering information on laboratory emergency preparedness, biosafety, biosecurity, and cybersecurity practices. Laboratories that have invested in contingency planning, disaster recovery, cybersecurity controls, and continuity-of-operations planning have valuable experiences that can help shape future expectations.

Why Should Laboratories Consider Submitting Comments?

Even as laboratory trade associations often comment publicly to speak on behalf of their members, individual laboratory perspectives remain extremely valuable. Regulators often rely on stakeholder comments to understand how proposed policies may affect real-world operations. Laboratories can provide practical insights regarding:

• Operational challenges
• Staffing limitations
• Technology adoption barriers
• Validation burdens
• Cost implications
• Rural access considerations
• Patient care impacts
• Quality and safety outcomes

The agencies have specifically encouraged input from a wide variety of stakeholders and noted that responses may help inform future CLIA rulemaking.

What Kind of Feedback Is Most Helpful?

The most effective comments are generally those that are data-driven, practical, and specific. Provide objective evidence whenever possible, explaining how laboratories actually perform testing today. CMS has organized the RFI into individual questions. Laboratories should respond directly to those questions and clearly identify the section being addressed. CMS specifically encourages commenters to organize responses according to the RFI structure. Your comments could help regulators better anticipate where laboratory medicine is heading rather than focusing solely on current practices, especially in areas particularly relevant for molecular and precision medicine laboratories. Many of the questions have significant implications for laboratories involved in precision medicine and advanced diagnostics.

Examples include:

• Performance specifications for NGS and other emerging technologies
• Validation considerations for MRD testing
• AI-supported interpretation of genomic results
• Responsibilities of data analysis and interpretation facilities
• Long-term retention of tissue specimens for future biomarker testing
• Qualifications and competency requirements for specialized personnel

Laboratories operating at the forefront of molecular diagnostics may have the greatest opportunity to help regulators understand how modern testing environments differ from those envisioned when CLIA regulations were originally drafted.

The Bottom Line

This RFI represents an opportunity for laboratories to help shape the next generation of CLIA oversight. CMS and CDC are actively asking whether current regulations adequately reflect modern laboratory medicine and what changes should be considered in future rulemaking. Laboratories that take the time to share their experiences can help ensure that future CLIA requirements promote innovation, maintain quality, support patient access, and reflect the realities of today’s rapidly evolving diagnostic landscape. With comments due by September 14, 2026, now is an ideal time for laboratory leaders to review the questions, identify areas relevant to their operations, and make their voices heard.

How to Submit Your Comments

When preparing submissions, laboratories should:

• Reference File Code CMS-3485-NC.
• Clearly identify the specific section and question number being addressed.
• Organize comments according to the structure of the RFI.
• Include examples, data, operational experience, and supporting evidence whenever possible.

Submission Options

Option 1: Submit Electronically (Preferred)

CMS encourages stakeholders to submit comments electronically through Regulations.gov: Docket: CMS-2026-2345

 Website: https://www.regulations.gov/docket/CMS-2026-2345

Follow the “Submit a Comment” instructions provided on the docket page.

Option 2: Submit by Regular Mail

Centers for Medicare & Medicaid Services
Department of Health and Human Services
Attention: CMS-3485-NC
P.O. Box 8016
Baltimore, MD 21244-8016

Note: CMS recommends allowing sufficient mailing time to ensure comments are received before the close of the comment period.

Option 3: Submit by Express or Overnight Mail

Centers for Medicare & Medicaid Services
Department of Health and Human Services
Attention: CMS-3485-NC
Mail Stop C4-26-05
7500 Security Boulevard
Baltimore, MD 21244-1850

Viewing Public Comments

Laboratories and other stakeholders can review comments submitted in response to the CLIA RFI throughout the comment period. CMS posts comments received before the deadline on Regulations.gov as soon as possible after receipt, allowing the public to see how laboratories, professional societies, healthcare providers, manufacturers, and other interested parties are responding to the agency’s questions. Comments can be viewed by visiting www.regulations.gov and searching for the docket associated with this RFI. Reviewing submitted comments can be a valuable exercise for laboratory leaders, providing insight into the perspectives of peers, professional associations, accreditation organizations, health systems, and diagnostic innovators. These comments may also help laboratories identify emerging areas of consensus, potential concerns, and policy recommendations that could influence future CLIA modernization efforts.

https://www.federalregister.gov/documents/2026/07/16/2026-14358/request-for-information-clinical-laboratory-improvement-amendments-of-1988-clia-regulations

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Stacey Gilbert, MPH, MBA
Director, Precision Medicine